美国北卡罗来纳大学黄力夫课题组报道用脂质体抗生素杀死肿瘤相关细菌产生新抗原，诱导抗肿瘤免疫反应。2023年9月25日出版的《自然—生物技术》杂志发表了这项成果。

在结直肠癌(CRC)患者中，他们发现针对厌氧菌的切除前抗生素可显着提高25.5%的无病生存率。在小鼠研究中，他们设计了一种包裹在脂质体中的抗生素银-替硝唑复合物(LipoAgTNZ)，以消除原发性肿瘤和肝脏转移中的肿瘤相关细菌，而不会引起肠道微生物群失调。由促瘤细菌(核梭杆菌)或益生菌(大肠杆菌)定殖的小鼠结直肠癌模型对LipoAgTNZ治疗有反应，使两种核梭菌感染的结直肠癌模型的长期存活率超过70%。

抗生素治疗产生微生物新抗原，引发抗肿瘤CD8+ T细胞。异源和同源细菌表位有助于免疫原性，启动T细胞识别感染和未感染的肿瘤。他们的策略以肿瘤相关细菌为目标，引发抗肿瘤免疫，为微生物组免疫治疗干预铺平道路。

研究人员表示，越来越多的证据表明，肿瘤微生物群是影响癌症进展的一个因素。

附：英文原文

Title: Killing tumor-associated bacteria with a liposomal antibiotic generates neoantigens that induce anti-tumor immune responses

Author: Wang, Menglin, Rousseau, Benoit, Qiu, Kunyu, Huang, Guannan, Zhang, Yu, Su, Hang, Le Bihan-Benjamin, Christine, Khati, Ines, Artz, Oliver, Foote, Michael B., Cheng, Yung-Yi, Lee, Kuo-Hsiung, Miao, Michael Z., Sun, Yue, Bousquet, Philippe-Jean, Hilmi, Marc, Dumas, Elise, Hamy, Anne-Sophie, Reyal, Fabien, Lin, Lin, Armistead, Paul M., Song, Wantong, Vargason, Ava, Arthur, Janelle C., Liu, Yun, Guo, Jianfeng, Zhou, Xuefei, Nguyen, Juliane, He, Yongqun, Ting, Jenny P.-Y., Anselmo, Aaron C., Huang, Leaf

Issue&Volume: 2023-09-25

Abstract: Increasing evidence implicates the tumor microbiota as a factor that can influence cancer progression. In patients with colorectal cancer (CRC), we found that pre-resection antibiotics targeting anaerobic bacteria substantially improved disease-free survival by 25.5%. For mouse studies, we designed an antibiotic silver-tinidazole complex encapsulated in liposomes (LipoAgTNZ) to eliminate tumor-associated bacteria in the primary tumor and liver metastases without causing gut microbiome dysbiosis. Mouse CRC models colonized by tumor-promoting bacteria (Fusobacterium nucleatum spp.) or probiotics (Escherichia coli Nissle spp.) responded to LipoAgTNZ therapy, which enabled more than 70% long-term survival in two F. nucleatum-infected CRC models. The antibiotic treatment generated microbial neoantigens that elicited anti-tumor CD8+ T cells. Heterologous and homologous bacterial epitopes contributed to the immunogenicity, priming T cells to recognize both infected and uninfected tumors. Our strategy targets tumor-associated bacteria to elicit anti-tumoral immunity, paving the way for microbiome–immunotherapy interventions.

DOI: 10.1038/s41587-023-01957-8

Source: https://www.nature.com/articles/s41587-023-01957-8